The Neuroscience of Traumatic Brain Injury

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Diagnosis and Treatment
of Traumatic Brain Injury
The Neuroscience of Traumatic Brain Injury

Edited by
Rajkumar Rajendram
Department of Medicine, King Abdulaziz Medical City, King Abdulaziz International Medical Research
Center, Ministry of National Guard - Health Affairs, Riyadh, Saudi Arabia
College of Medicine, King Saud bin Abdulaziz University of Health Sciences, Riyadh, Saudi Arabia

Victor R. Preedy
King’s College London, London

Colin R. Martin
Institute for Health and Wellbeing, University of Suffolk, United Kingdom
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 Dedication

I dedicate this book to my wonderful daughter, Dr. Caragh Brien,

of whom I am so incredibly proud.
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Contents

Contributors xix Prognostic models 21

Preface xxv Epidemiological considerations: the
importance of outcome prediction
considering between-country differences 21
Section A Approaches to predictive models in TBI:
Discordance between clinical research
Setting the scene and introductory and clinical management of TBI 22
chapters Recommendation for developing a
predictive model in TBI 22
1. Traumatic brain injury and Applications to other areas of neuroscience 22
in-hospital mortality- CT perfusion Mini-dictionary of terms 23
and beyond Key facts of potential strategies in TBI
outcome research 23
Sudharsana Rao Ande and Jai Jai Shiva Shankar
Summary points 24
Introduction 3 References 24
Neuroimaging for TBI 4
Plain head computed tomography (CT) 5 3. Thirty years post-injury: Impact
CT angiography (CTA) 6 of traumatic brain injury on later
CT perfusion 7 Alzheimer’s disease
Magnetic resonance perfusion
(MR perfusion) 7 Hiraoka Takashi and Hanayama Kozo
Diffusion tensor imaging 8 Introduction 27
CT perfusion and in-hospital mortality 8 Understanding traumatic brain injury as a
Applications to other areas of neuroscience 10 risk factor for Alzheimer’s disease 28
Mini-dictionary of terms 11 Similarities in the long-term prognosis
Key facts of TBI 11 of mild repetitive and severe isolated
Summary points 11 traumatic brain injury 28
References 12 Post-traumatic brain injury Alzheimer’s
disease 29
2. Predictors of outcome in Amyloid-β pathology in traumatic brain
moderate and severe traumatic injury 30
brain injury Tubulin-associated unit pathology in
traumatic brain injury 31
Rosalia Zangari, Paolo Gritti, and
Applications to other areas of
Francesco Biroli
neuroscience 31
Introduction 15 Mini-dictionary of terms 34
Predictors and outcome measures 16 Key facts of post-traumatic brain injury
Acute predictors 16 delayed-onset cognitive and psychiatric
Sub-acute predictors 20 disorders 35
ICU neuromonitoring 20 Summary points 35
Biomarkers 20 Acknowledgments 36
Pediatric TBI 21 References 36

vii
viii  Contents

4. Drug interventions and stem Sedation and analgesia 65

cells in traumatic brain injury: Seizure management 65
Translation from experimental Corticosteroids 65
Calcium channel blockers 65
model to bedside
Conclusions and future directions 66
Maha Tabet, Mohammad Amine Reslan, Case 1 66
Muhammad Ali Haidar, Hawraa Issa, Maya Case 2 66
El Dor, Reem Abedi, Leila Nasrallah, Ali Eid, Applications to other areas of neuroscience 67
Kazem Zibara, and Firas H. Kobeissy Mini-dictionary of terms 67
Key facts of advanced trauma life support 67
Introduction 40
Summary points 68
The pathophysiology of TBI 40
References 68
Possible treatments for TBI: Drug
interventions 40
Introduction to stem cells and their 6. Neuropsychiatric disorders after
therapeutic potential 45 severe traumatic brain injury: An
Pre-clinical studies utilizing stem cells for overview
the treatment of TBI 45
Clinical studies utilizing stem cells 47 Dolores Villalobos, Umberto Bivona,
Limitations of stem cells use 47 and Maria Paola Ciurli
Application to other fields of neuroscience 51 Introduction 71
Mini-dictionary of terms 51 The role of brain injury severity and
Key facts of stem cells 51 structural pathophysiologic changes 72
Summary points 51 The role of post-injury variables 73
References 52 The role of pre-morbid variables 73
The role of environmental variables 74
5. Management of traumatic Methodological issues related to the
brain injury from the aspect of neuropsychiatric assessment 74
emergency department and case studies Classification of the main neuropsychiatric
disorders 75
Bedriye Müge Sönmez
Agitation 75
Introduction 58 Aggression 76
Emergency department considerations 58 Irritability 76
Management of mild brain injury Disinhibition 76
(GCS score 13–15) 59 Substance abuse disorders 76
Management of moderate TBI 59 Depression and apathy 76
Management of sTBI 60 Anxiety and post-traumatic stress disorder
Airway 60 (PTSD) 76
Rapid sequence intubation 60 Psychosis, bipolar disorder,
Breathing 61 obsessive-compulsive symptoms 77
Circulation 62 Sleep disturbances 77
Disability 62 A brief consideration of possible
Medical treatment of brain injury 62 interventions 78
Intravenous fluids 62 Conclusion 78
Correction of anticoagulation 63 Applications to other areas of
Tranexamic acid 63 neuroscience 78
Transfusion in TBI 64 Mini-dictionary of terms 79
Management of elevated ICP 64 Key facts of neuropsychiatric disorders
Body positioning 64 after severe traumatic brain injury:
Hyperosmolar agents 64 An overview 80
Hyperventilation 64 Summary points 80
Temperature management 64 References 80
 Contents  ix

Section B Key facts about fibrinogen 107

Summary points 107
Clinical features of traumatic brain References 108
injury
9. Linking traumatic brain injury
7. Cerebral hemorrhages in and nosocomial infections
traumatic brain injury
Marwan Bouras, Karim Asehnoune,
Andrei Irimia, Kenneth A. Rostowsky, and Antoine Roquilly
E. Meng Law, and Helena C. Chui
Introduction 111
Introduction 88 Post-traumatic immunosuppression 112
The BBB and NVC after TBI 88 Post-traumatic critical illness-related
NVC, TBI, and aging 88 corticosteroid insufficiency 114
Vascular pathophysiology after TBI 89 Post-traumatic dysbiosis 114
TBI hemorrhage identification and Glucocorticoids: A therapeutic avenue
localization 89 in the prevention of nosocomial
Differential etiology of TBI-related infections after trauma 115
hemorrhages 91 Application to other areas of neuroscience 118
(Epi)genetic risk for hemorrhage after Mini-dictionary of terms 118
experimental TBI 92 Key facts of ventilatory-associated
Novel approaches for TBI CMB pneumonia 118
neuroimaging CMBs 92 Summary points 119
TBI hemorrhages and AD 94 References 119
Applications to other areas of
neuroscience 95 10. Long-term sequelae of
Mini-dictionary of terms 96
mild-repetitive and severe
Key facts of cerebral hemorrhages after
traumatic brain injury 96
traumatic brain injury: Clinical
Summary points 97
manifestations, neuropathology
Acknowledgments 97 and diagnosis by tau PET imaging
References 97 Keisuke Takahata, Kenji Tagai, Makoto Higuchi,
and Masaru Mimura
8. Linking fibrinogen, coagulopathy Introduction 123
prophylaxis, and traumatic brain injury Clinical symptoms and neuropathology
of chronic states of TBI 124
Ryuta Nakae and Shoji Yokobori
Growing need for neuroimaging biomarkers
Introduction 101 of chronic pathologies of TBI 127
Fibrinogen 102 PET imaging of TBI with first-generation
TBI-induced coagulation/fibrinolysis tau PET tracers 127
cascade 102 Challenges for quantification of tau load
Time course of fibrinogen concentration in TBI by tau PET imaging 128
in the acute phase of TBI 103 Development of second-generation
Fibrinogen concentration and outcome tau PET tracer 130
in TBI 105 PET imaging of TBI with second-generation
Therapeutic target level of fibrinogen 105 tau PET tracer 130
Measurements of fibrinogen 105 Future directions of research 132
Correlation between fibrinogen and Conclusion 132
fibrinolytic parameters 106 Applications to other areas of neuroscience 132
Treatment by replenishment of fibrinogen 106 Key facts of neurodegenerative diseases
Applications to other areas of neuroscience 106 following TBI 132
Mini-dictionary of terms 107 Key facts of tau PET imaging 133
x  Contents

Mini-dictionary of terms 133 Disruptions following TBI 157

Summary points 133 Brain network disruption following TBI 157
Acknowledgments 133 Deficits in attention and inhibition
References 133 following TBI 157
Deficits in working memory
11. Evaluating the integrity of white following TBI 159
matter after traumatic brain injury Structural and functional changes
and the utility of diffusion tensor following TBI 161
imaging Cortical thickness 161
Cortical-striatal loop 161
Eunkyung Kim, Min-Gu Kang, and Modulating cortical activations in TBI
Byung-Mo Oh using non-invasive brain stimulation 161
Introduction 137 Applications to other areas of neuroscience 163
The vulnerable white matter tracts in TBI 138 Mini-dictionary of terms 164
Clinical and neurophysiological evaluation Key facts of working memory and attention 165
of injury to white matter 138 Summary points 165
Key facts of clinical and neurophysiological References 165
assessment after TBI 139
DTI: A primer 140 13. Traumatic brain injury: Linking
DTI and the white matter integrity 140 intracranial pressure, arterial
Key facts of DTI 141 pressure, and the pressure
DTI sequences and analysis tools: Strengths reactivity index
and weaknesses 141
Alwyn Gomez, Carleen Batson, Logan Froese,
Moderate-to-severe TBI: DTI Study 142
and Frederick A. Zeiler
DTI in special populations: Mild TBI and
blast-induced TBI 142 Introduction 170
Diffusion tensor tractography (DTT) in Cerebral autoregulation 170
patients with TBI 143 Development of the pressure reactivity
Limitation of DTI as a clinical tool 144 index (PRx) 170
Conclusion 146 Association of PRx with outcomes 172
Applications to other areas of neuroscience 146 Global outcomes following TBI 172
Mini-dictionary of terms 146 PRx thresholds 174
Summary points 147 PRx and imaging findings 175
References 147 PRx and cerebral oxygen metabolism 175
PRx in targeted therapy 176
12. Cerebral activation of attention Limitation of PRx 176
and working memory in traumatic Future of cerebrovascular reactivity 176
brain injury Application to other areas of neuroscience 177
Mini-dictionary of terms 177
Athena Stein, Kartik K. Iyer, and Key facts of cerebrovascular reactivity in TBI 177
Karen M. Barlow Summary points 178
Introduction: Executive dysfunction in Acknowledgments 178
traumatic brain injury 151 References 178
The neural basis of attention and working
memory 152 14. Cerebral perfusion pressure
The dual-network model of attention 153 thresholds in traumatic brain injury
Inhibitory control 153
Alwyn Gomez, Carleen Batson, Logan Froese,
Working memory 155
and Frederick A. Zeiler
Developmental changes in brain networks 156
Maturation of attention networks 156 Introduction 182
Maturation of inhibition 157 Defining cerebral perfusion pressure 182
Maturation of working memory 157 Cerebral autoregulation 182
 Contents  xi

CBF variability in TBI 183 Prognostic indicators 208

CPP targets in TBI 183 Clinical predictive factors 208
Global CPP targeted therapy 184 Evaluation scales 209
Personalized CPP targets 185 Instrumental diagnostic and prognostic
ARDS in TBI 186 indicators 210
Future directions 186 Neurophysiology 210
Applications to other areas of neuroscience 187 Neuroimaging 211
Mini-dictionary of terms 187 Sequelae of severe Acquired BRAIN Injury (sABI) 211
Key facts of CPP thresholds in TBI 188 Post-traumatic amnesia 211
Summary points 188 Intervention—A multidisciplinary approach 212
Acknowledgments 188 Pharmacotherapeutic approach 213
References 188 Applications to other areas of neuroscience 214
Neurophysiology and neuroimaging 214
15. Brain swelling in traumatic brain injury Neuropsychology 214
Silvia De Rosa, Lucia Cattin, Luca Ricciardi, Neurorehabilitation 215
and Alba Scerrati Mini-dictionary of terms 215
Key facts of post-coma syndrome 215
Introduction 191 Summary points 215
Historical background 191 References 216
Overview on the blood–brain barrier 192
The pathogenesis of brain edema 192
Cytotoxic edema 194 Section C
Vasogenic edema 194
Diagnosis and evaluation
Clinical translation 195
Clinical classification 196
17. Features of the World Health
Focal/perifocal traumatic brain swelling 197
Diffuse/global traumatic brain swelling 197
Organization Disability
Mild/moderate TBI (GCS>8) 197 Assessment Schedule 2.0 and its
Severe TBI (GCS≤8) 199 applications for traumatic brain
Conclusion(s) 199 injury assessment
Applications to other areas of neuroscience 200 Yu-Hao Lee, Shih-Wei Huang,
Mini-dictionary of terms 200 and Tsan-Hon Liou
Key facts of cerebral edema 200
Summary points 200 Introduction 223
Acknowledgments 201 ICF framework 224
Conflict of interest 201 WHODAS 2.0 224
References 201 Reliability 228
Validity 228
16. Post-coma syndrome in the context Current research on the use of the
of severe acquired brain injury: WHODAS 2.0 in TBI care 228
Traumatic brain injury and beyond Comparison of disability in spinal cord
injury and TBI, as assessed using the
Rita Formisano, Marta Aloisi, and
WHODAS 2.0 228
Marianna Contrada
Evaluation of post-concussion syndrome in
Definition issues 206 patients with mild TBI 228
Severe acquired brain injury 206 Association between history of lifetime TBI
Disorders of consciousness 206 and disabling functional restrictions 228
Coma206 Assessment of chronic TBI with the
Vegetative State/Unresponsive Wakefulness WHODAS 2.0 228
Syndrome 207 Psychometric properties of the WHODAS 2.0 229
Minimally Conscious State (MCS) 207 Prediction of institutionalization among
Functional Locked-in Syndrome 208 patients with TBI 229
Covert cognition 208 Conclusion 229
xii  Contents

Applications to other neuroscience fields 229 Evaluation of the prospective power of

Mini-dictionary of terms 229 autoantibodies as prognostic markers
Key facts of the World Health Organization in TBI 245
Disability Assessment Schedule 2.0 230 B-lymphocytes as a therapeutic target
Summary points 230 post-TBI 246
References 230 Conclusion 246
Applications to other areas of neuroscience:
18. Biomarkers in pediatric traumatic The efficacy of GFAP in assessing the
injury: The brain and beyond diagnostic power of different neuroimaging
modalities 247
Dimitrios Metaxas, Georgios Alexiou, Mini-dictionary of terms 247
Olga Ygropoulou, Dimitrios Rizos, Key-facts of TBI biomarkers 248
and Spyridon Voulgaris Key facts of the glymphatic system (GS) 248
Introduction 233 Summary points 248
Biomarkers in traumatic brain injury 234 References 248
Biomarkers in pediatric traumatic brain
injury 234 20. Chitinase-3-like protein 1:
Biomarkers and neuroimaging 234 Features and applications as a
Biomarkers as predictors of severity and biomarker in traumatic brain injury
prognosis of TBI 235
C.S. Carabias and A. Lagares
Biomarkers predicting late sequalae of TBI
in children 235 Introduction 252
Recognizing abusive trauma 236 Preclinical studies of YKL-40 in TBI 253
Applications to other areas of neurosciences 236 Pericontusional astrocytic YKL-40
Mini-dictionary of terms 236 transcription is driven by cytokines
Key facts of traumatic brain injury 236 released from macrophages infiltrating the
Key facts of biomarkers 236 necrotic area 253
Summary points 237 CHI3L1: Friend or foe following TBI? 253
References 237 CHI3L1 is not involved in the ultrastructural
characteristics of TBI lesions 260
19. Brain injury biomarkers: Proteins YKL-40 may play a role in immune cell
and autoantibodies interplay trafficking into the injured brain 260
CHI3L1 is a potential pathological
Samar Abdelhady, Hawraa Issa,
fingerprint of blast-induced neurotrauma 261
Ohanes Ashekyan, Muhammad Ali Haidar,
Clinical studies of YKL-40 in TBI 261
Oumaima Outani, Yasmine Samir, Eslam Belal,
Release patterns of CSF YKL-40 are related
Zaynab Shakkour, Stefania Mondello,
to the trauma-induced pro-inflammatory
and Firas H. Kobeissy
response that negatively impacts patient
Introduction 240 clinical outcomes 261
The immunological cascade of events CSF YKL-40 levels as a reflection of post-
post-TBI 240 concussion syndrome severity 264
Innate immune response in TBI: A tug YKL-40 concentration as an objective and
of war between pro- and complementary assessment of impairment
anti-inflammatory mediators 240 of consciousness levels and radiologic
Astrocyte-derived immunomodulatory lesion burden in head injury patients 264
mechanisms post-TBI 241 Future directions 272
Adaptive immune response in TBI: Applications to other areas of
The role of T- and B-lymphocytes 241 neuroscience 272
The glymphatic system disruption: Mini-dictionary of terms 272
A source of biomarkers in TBI 242 Key facts of CHI3L1: Features and
Autoantibodies as biomarkers in TBI: applications as a biomarker in TBI 273
An overview 243 Summary points 273
A list of identified autoantibodies post-TBI 243 References 273
 Contents  xiii

21. microRNA biomarkers in traumatic Cerebrovascular disorders in severe

brain injury: A new narrative traumatic brain injury 306
Hypoperfusion 307
Steven D. Hicks Vasospasm 308
Introduction 277 Hyperemia 309
Characteristics of the ideal biomarker 277 TCD peculiarities in certain clinical forms of
Unique properties of micro-ribonucleic acids traumatic brain injury 309
(miRNAs) 278 TCD-patterns at cerebral contusions 309
Measurement of miRNAs 279 TCD-patterns at traumatic ICH 310
The response of miRNAs to TBI 280 TCD-patterns after surgical removal of ICH 311
Use of miRNAs for mTBI diagnosis 280 Applications to other areas of neuroscience 311
Predicting TBI outcomes with miRNAs 281 Mini-dictionary of terms 312
Clinical management of mTBI 282 Key facts of transcranial Doppler ultrasound 312
Top miRNA candidates 282 Summary points 312
Future directions for miRNA research in TBI 283 References 312
Applications to other areas of neuroscience 284
Mini-dictionary of terms 285 24. Computed tomography
Key facts of micro-ribonucleic acids (miRNAs) 285 assessment of brain swelling
Summary points 285
Matheus Fernandes de Oliveira, Anselmo Alves
Conflicts of interest 286
Boa Sorte, Jr, and Gustavo Fernandes Leobas
References 286
Introduction 315
22. Pediatric minor head injury imaging Parameters to evaluate brain swelling
in computed tomography 316
Anastasios Nasios, Spyridon Voulgaris,
Marshall scale 319
and George Alexiou
Rotterdam scale 320
Introduction 289 Criteria to guide practical management 321
Epidemiology of pediatric traumatic Special conditions 322
brain injury (pTBI) 289 Applications to other areas of neuroscience 323
Types of injury in the pediatric population 289 Key facts of brain swelling and computed
Minor pTBI features 290 tomography 323
Imaging 291 Mini-dictionary of terms 323
Imaging techniques available in pTBI 291 Summary points 323
Conventional imaging techniques 292 References 324
Advanced imaging techniques 294
Applications to other areas of neuroscience 296 25. Machine learning and prediction
Mini-dictionary of terms 296 of traumatic brain injury mortality
Key facts of concussions 297
João Gustavo Rocha Peixoto dos Santos
Summary points 297
and Wellingson Silva Paiva
References 297
Introduction 327
23. Transcranial Doppler ultrasound TBI mortality 328
in acute traumatic brain injury Predicting TBI mortality 328
Predictors of outcome 328
Alexey O. Trofimov, Anatoly Y. Sheludyakov,
Admission characteristics 329
Andrew Y. Abashkin, Darya I. Agarkova,
Clinical course 329
Michael Dobrzeniecki, Zhanna B. Semenova,
Outcomes 330
and Denis E. Bragin
Prognostic models 330
Introduction 301 Building a prognostic model 330
Physical basis for transcranial Doppler Important prognostic models 331
ultrasound 302 Machine learning 333
Technical features and ultrasound Conclusions 334
neurovascular anatomy 302 Applications to other areas of neuroscience 334
xiv  Contents

Mini-dictionary of terms 334 Other areas of neuroscience 364

Key facts of quality of life of patients after TBI 335 Discussion 364
Key facts of Glasgow coma scale score 335 Mini dictionary terms 365
Key facts of pupillary abnormalities 335 Key facts of adherence of guidelines
Key facts of abbreviated injury score (AIS) 335 for treatment of severe head injury 365
Key facts of CT Marshall classification 335 Summary points 365
Summary points 336 References 365
References 336 Further reading 366

26. Pituitary dysfunction after 28. Anesthesia in traumatic brain injury

traumatic brain injury: A focus on Siddharth Chavali and Girija Prasad Rath
screening, diagnosis, and treatment
Introduction 367
Aysa Hacioglu, Zuleyha Karaca, and Preoperative management 367
Fahrettin Kelestimur Pathophysiology 367
Introduction 339 Airway management 368
Screening of pituitary dysfunction following Systemic complications of brain injury 368
traumatic brain injuries 340 Anesthetic management 369
Predictive factors of post-TBI pituitary Neuropharmacology of commonly used
dysfunction 340 anesthetic agents 370
Screening algorithms of pituitary Autoregulation and anesthetic agents 372
dysfunction after traumatic brain injuries 341 Hemodynamic management 372
Diagnosis of pituitary dysfunction following Management of intraoperative intracranial
traumatic brain injuries 344 hypertension 373
Central adrenal insufficiency 344 Intraoperative monitoring 374
Growth hormone deficiency 344 Postoperative sequelae 374
Central hypogonadism 345 Anesthetic agents and neuronal injury 374
Central hypothyroidism 345 Applications to other areas of neuroscience 375
Central diabetes insipidus 346 Mini-dictionary of terms 375
Treatment of pituitary dysfunction following Key facts of anesthetics for injured brain 376
traumatic brain injuries 346 Summary points 376
Central adrenal insufficiency 346 References 376
Growth hormone deficiency 348
Central hypogonadism 348
29. Treatment of raised intracranial
Central hypothyroidism 349 pressure in traumatic head injury
Central diabetes insipidus 349 Alvaro Cordoba and Bernardina Frache
Applications to other areas of neuroscience 349
Mini-dictionary of terms 350 Introduction 379
Key facts of screening strategies, diagnostic Analysis of the treatment during the
and treatment modalities of pituitary so called “brain decade” 379
dysfunction after traumatic brain injury 350 Recommendations 381
Summary points 350 Intracranial pressure monitoring 382
References 351 Current data update and analysis 382
Role of the cranial decompression 384
Corticosteroids 385
Progesterone 385
Section D Erythropoietin 385
Treatments: Experimental and clinical Amantadine 386
Tranexamic acid 386
27. European aspects of guidelines Citicoline 386
used in traumatic brain injury Anti-inflammatory therapies 386
Role of the ultrasound. Transcranial
Alvaro Cordoba, Bernardina Frache,
Doppler TCD 386
and Jose Maria Dominguez Roldan
Hypothermia 387
Introduction 357 Discussion 387
Current data update and analysis 360 Applications in other areas of neuroscience 387
 Contents  xv

Mini dictionary terms 393 Overview of traumatic brain injury and

Key facts 393 hyperosmolar therapy 422
Summary points 393 Cerebral edema 422
References 393 Traumatic brain injury-associated cerebral
Further reading 395 edema 423
Use of hyperosmolar therapy in TBI 424
30. Seizures after traumatic brain History and evolution of the use of HTS
injury and their treatment for TBI 424
Pathophysiology/mechanism of HTS use
Luiz Fernando Freire Royes, Michele Rechia
for TBI 424
Fighera, Ana Flavia Furian, M.S. Oliveira,
Current use of HTS in the pediatric clinical
Leonardo Magno Rambo, and Gabriel
setting 425
Corrêa Lima
Indications 425
Introduction 397 Contraindications 426
Pathophysiology of TBI-induced Dosing 426
epileptogenesis 399 Monitoring 426
Epidemiological and clinical presentation 399 Potential adverse effects 427
Translational considerations of PTE Literature review 427
mechanisms 400 Applications to other areas of neuroscience 427
Pre-clinical studies in animal models of PTE 402 Mini-dictionary of terms 432
Early intervention after TBI to prevent PTS Key facts of TBI in children 433
and PTE 403 Summary points 433
Conclusions 406 References 433
Applications to other areas of neuroscience 406
Mini-dictionary of terms 406
33. Treatment of vascular lesions in
Kay facts of post-traumatic epilepsy (PTE) 407
Summary points 407
traumatic brain injury
References 407 Alvaro Cordoba

31. Neurosurgical treatment of critical Arterial lesions: Dissections and

brain damage: The early post- pseudoaneurysms 437
Endovascular treatment of traumatic
surgical period and algorithms
aneurysms 438
Alexey O. Trofimov, Anatoly Y. Sheludyakov, Therapeutic arterial occlusion 438
Andrew Y. Abashkin, Darya I. Agarkova, Artem Mechanical thrombectomy 440
A. Kopylov, Svyatoslav B. Korolev, Michael Stenting 440
Dobrzeniecki, Xenia A. Trofimova, Carotid-cavernous fistula 441
Denis E. Bragin, and Dmitry S. Martynov Treatment 443
Conservative 443
Introduction 411
Surgical management 443
Critical damage: Physiological features and
Radiosurgery 443
surgical treatment nuances 412
Endovascular management 443
“Damage control”: A path between the
Applications to other areas of neuroscience 446
Scylla and the Charybdis 413
Mini-dictionary of terms 446
Applications to other areas of neuroscience 416
Key facts: Treatment of vascular lesions
Mini-dictionary of terms 417
in traumatic head injury 446
Key facts of the surgical treatment of
Summary points 447
polytraumazed patient with TBI 417
References 447
Summary points 417
Further reading 448
References 418

32. Hypertonic saline usage in 34. Airway pressure release ventilation

traumatic brain injury: A focus on (APRV) in traumatic brain injury
pediatrics Christopher S. Thomas and Evert A. Eriksson
Andrew Wu, Tina Slusher, and Andrew Kiragu
Introduction 449
Introduction 421 Airway pressure release ventilation 449
xvi  Contents

Positive end expiratory pressure and cerebral Cannabidiol in TBI-related gut microbiota
perfusion pressure 450 dysfunctions 470
APRV in traumatic brain injury 450 Cannabidiol and clinical trials 470
Conclusion 451 Applications to other areas of neuroscience 472
Applications to other areas of neuroscience 452 Mini-dictionary of terms 472
Mini-dictionary of terms 452 Key facts of cannabidiol 473
Key facts of APRV in traumatic brain injury 452 Summary points 473
Summary points 452 References 473
References 453
37. Valproic acid: A new narrative
35. Linking death, the paranasal
on its features and effects in
sinuses, and traumatic head trauma
traumatic brain injury
Ayhan Kanat and Elena Romana Gasenzer
Glenn Wakam, Michael Kemp, and Hasan Alam
Introduction 455
Background 477
The significance of the paranasal sinuses 455
Epigenetic changes following TBI 478
Anatomy of paranasal sinuses 455
Valproic acid: A histone deacetylase inhibitor 479
Frontal sinus 455
Effects of valproic acid in pre-clinical models
Management: A change in surgical paradigm 456
of traumatic brain injury 479
Sphenoid sinus 456
Underlying mechanisms of
Maxillary sinus 456
VPA-neuroprotection 479
Cribiform plate fractures 457
Dosing, safety, and future work 482
History and physical examination 457
Applications to other areas of neuroscience 482
Imaging of paranasal sinus trauma 457
Mini-dictionary of terms 482
Pathogenesis 457
Key facts of traumatic brain injury and
Cerebral perfusion pressure 458
valproic acid 482
Oxidative stress 459
Summary points 482
Blood–brain barrier disruption 459
References 483
The debate about the protective effect
of the paranasal sinuses 459
Music and paranasal sinus 459 38. Dietary supplementation for
Conclusion 459 traumatic brain injury
Applications to other areas of
Muthu Kumaradoss MohanMarugaRaja,
neuroscience 460
Agilandeswari Devarajan, and Vipin V. Dhote
Mini-dictionary of terms 460
Key facts of paranasal sinuses 460 Introduction 485
Key facts of crumple zone 460 Omega-3 fatty acids 486
Summary points 460 Creatine 488
References 460 Vitamins 489
Zinc 489
36. Cannabidiol in traumatic brain injury Magnesium 489
Other dietary supplements for TBI 489
Enza Palazzo, Monica Iannotta, Carmela Belardo,
Promising dietary supplements for TBI 490
Rosmara Infantino, Flavia Ricciardi, Serena
Conclusion 490
Boccella, Francesca Guida, Livio Luongo,
Applications to other areas of neuroscience 490
and Sabatino Maione
Mini-dictionary of terms 491
Introduction 464 Key facts of dietary supplementation
Cannabidiol targets 465 for traumatic brain injury:
Phytocannabinoids 465 Omega-3 fatty acids 491
Neuroprotective role of cannabidiol 468 Key facts of dietary supplementation
Cannabidiol in TBI-related anxiety and for traumatic brain injury: Sports
depression 469 induced TBI 492
Cannabidiol in TBI and post-traumatic stress Summary points 492
disorder-related aggression 470 References 492